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F Seibold

Publications and source records attributed to F Seibold.

30 records · Page 2Linked to original sources
PubMed1998

pANCA represents a cross-reactivity to enteric bacterial antigens.

pANCA (perinuclear antineutrophil cytoplasmic antibodies) occur at a high frequency in patients with ulcerative colitis. The purpose of this study was to investigate the frequency of pANCA in different mouse models of colitis and to determine whether there is any cross-reactivity of pANCA with bacterial antigens. Sera from 146 colitic mice and controls and from 30 patients with ulcerative colitis were tested for the presence of pANCA by indirect immunofluorescence with or without prior absorption with homogenized murine cecal bacteria. pANCA was found in 24 of 36 IL10(-/-) mice. In contrast to the human pANCA, both nuclear and perinuclear staining was found. Absorption of either human or mouse pANCA-positive sera with enteric bacterial antigens greatly reduced or abolished the specific perinuclear staining of pANCA. We conclude that pANCA occurs not only in humans but also in IL19(-/-) mice with colitis and likely represents a cross-reactivity with enteric bacterial antigens.

Animals↗
PubMed1997

Pancreatic autoantibodies in Crohn's disease: a family study.

BACKGROUND: Pancreatic antibodies occur in about one third of patients with Crohn's disease. AIMS: To evaluate the relevance of pancreatic antibodies as a genetic marker in patients with Crohn's disease and their first degree family members and spouses. To characterise further pancreatic antibodies by assessment of IgG subclasses. METHODS: Six hundred and fifty serum samples were tested for pancreatic antibodies by immunofluorescence on sections of human pancreas. Incidence of pancreatic antibodies and their subtypes were studied on 212 serum samples from patients with Crohn's disease. In the familial study, 72 patients with Crohn's disease and 196 first degree family members and 26 patients with ulcerative colitis and 90 first degree family members were included. Ten healthy families served as controls. RESULTS: Pancreatic antibodies were found in 58 (27%) of the patients with Crohn's disease and in none of the controls. Thirty patients had pancreatic antibodies of subtype I characterised by a drop-like fluorescence in the pancreatic acini, 28 patients had subtype II with a fine speckled staining in the acinar cells. Pancreatic antibodies of subtype I were both IgG1 and IgG2 antibodies by contrast with subtype II which were mainly of IgG1 subclass. Only five of 196 first degree relatives of patients with Crohn's disease had pancreatic antibodies. Four of these people had anamnestic data compatible with inflammatory bowel disease. Further investigations showed Crohn's disease in two of these people. In families with more than one member positive for pancreatic antibodies, pancreatic antibodies were of the same subtype in all cases. CONCLUSIONS: Pancreatic antibodies are a specific marker for Crohn's disease. Two subgroups of pancreatic antibodies can be distinguished by their pattern and immunoglobulin subclasses. Pancreatic antibodies rarely occur in family members of patients with Crohn's disease. These family members may also have Crohn's disease.

Autoantibodies↗
PubMed1997

Autoimmune hepatitis in inflammatory bowel disease: report of two unusual cases.

Elevated transaminases occur in up to 17% in patients with inflammatory bowel disease. Primary sclerosing cholangitis (PSC) is an important cause for elevated liver enzymes in these patients whereas autoimmune hepatitis is rare. Both diseases can overlap. We report two patients with an autoimmune hepatitis. One patient had Crohn's disease and arthritis with morphological liver changes typical for autoimmune hepatitis but without the characteristic autoantibody pattern. The other patient suffered from ulcerative colitis. He had antinuclear and antiactin antibodies as in autoimmune hepatitis type I. however, histological examination of the liver showed bile duct changes. Transaminases declined significantly in both patients after onset of steroid treatment. Therefore, the diagnosis of autoimmune hepatitis in patients with inflammatory bowel disease must not be missed, as immunosuppressive therapy improves the prognosis of the illness.

Adolescent↗
PubMed1996

Impaired pancreatic function in patients with Crohn's disease with and without pancreatic autoantibodies.

Pancreatic autoantibodies (PABs) are found in 31% of patients with Crohn's disease (CD), but they do not correlate with the activity of intestinal disease or the incidence of acute pancreatitis. Exocrine pancreatic insufficiency has been observed in patients with CD. The aim of our study was to correlate the occurrence of PABs with exocrine pancreatic function to explore the clinical significance of these antibodies. Serum samples of 64 patients with CD were tested for PABs by indirect immunofluorescence. In addition, all patients were tested for exocrine pancreatic insufficiency by a fluorescein dilaurate test. PABs were detected in 26 of 64 patients (40%). The PAB-positive and -negative groups did not differ in clinical characteristics, such as age, sex, involvement of intestine, previous surgical interventions, drug therapy, and disease activity. Seven of the antibody-positive patients (27%) had impaired pancreatic function, in contrast to three of 38 PAB-negative patients (8%) (p < 0.05). In conclusion, exocrine pancreatic function is impaired significantly more often in PAB-positive than in PAB-negative patients. A prospective follow-up is required to determine whether PAB-positive patients are more likely to develop pancreatic insufficiency later in their course of disease.

Adolescent↗
PubMed1996

Polymyositis, alopecia universalis, and primary sclerosing cholangitis in a patient with Crohn's disease.

We report a 36-year-old man with Crohn's disease, primary sclerosing cholangitis, and alopecia universalis. Six years after the onset of intestinal disease, the patient developed severe muscular pain and weakness of the neck. Muscle biopsy revealed myositis. Immunosuppressive treatment led to a significant improvement of muscular symptoms. Myositis in inflammatory bowel disease appears to be an important differential diagnosis in corticoid myopathy. Both alopecia and polymyositis are rarely associated with inflammatory bowel disease; thus, they have to be discussed as extraintestinal manifestations.

Adult↗
PubMed1996

Neutrophil antibodies (pANCA) in chronic liver disease and inflammatory bowel disease: do they react with different antigens?

OBJECTIVE: A high frequency of perinuclear neutrophil antibodies (pANCA) has been described in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We evaluated the presence of pANCA in chronic liver disease and compared the immunoglobulin G (IgG) subclasses of pANCA in inflammatory bowel disease with chronic liver disease. Since the antigen reacting with pANCA could not be determined, the antigenic role of various neutrophil antigens was evaluated. SUBJECTS AND METHODS: Detection of pANCA and their IgG subclass was performed by immunofluorescence. One hundred and forty patients with chronic liver disease, 96 patients with inflammatory bowel disease and 40 healthy controls were tested for pANCA. pANCA positive and negative sera were evaluated for their reactivity with different neutrophil antigens in an enzyme-linked immunosorbent assay (ELISA) system. RESULTS: pANCA were found in 8 of 23 patients (35%) with autoimmune hepatitis, in 6 of 21 patients (28%) with primary biliary cirrhosis (PBC), in 18 of 25 patients (72%) with PSC, in 3 of 48 patients (6%) with viral hepatitis, in 30 of 48 patients (62%) with UC, and in 2 of 48 patients (4%) with Crohn's disease. All 20 patients with alcoholic liver disease and 40 healthy controls were negative for pANCA. In contrast to the patients with UC who had 83% IgG1 and only 13% IgG3 antibodies, patients with PSC and PBC had an overexpression of IgG3 antibodies (PSC: 50% IgG3; PBC: 67% IgG3). A proportion of pANCA positive sera recognized lactoferrin, myeloperoxidase, cathepsin G, laminarase and alpha 1-antitrypsin. CONCLUSION: pANCA is not present only in patients with UC but in autoimmune liver diseases such as PSC, autoimmune hepatitis and PBC. Considering the IgG subclass of pANCA, the antibody response of patients with UC is different from patients with liver disease. No unique pANCA specific antigen could be detected, so heterogeneity of pANCA has to be considered.

Adolescent↗
PubMed1994

Neutrophil autoantibodies: a genetic marker in primary sclerosing cholangitis and ulcerative colitis.

BACKGROUND/AIMS: Perinuclear antineutrophil cytoplasmic antibodies (pANCA) were found at high frequency in patients with primary sclerosing cholangitis and ulcerative colitis. In this study, to accumulate further evidence for the importance of genetic factors in pathogenesis of inflammatory bowel disease, sera of patients with inflammatory bowel disease and primary sclerosing cholangitis and their unaffected family members were tested for pANCA. METHODS: Three hundred twenty-seven sera from 11 families of patients with primary sclerosing cholangitis, 43 families of patients with ulcerative colitis, 11 families of patients with Crohn's disease, and 11 healthy families were tested for pANCA in immunofluorescence on cytospin slides with isolated neutrophils. RESULTS: pANCA were found in 82% of the patients with primary sclerosing cholangitis and in 25% of their relatives. In ulcerative colitis, 70% of the patients and 30% of their relatives had pANCA. pANCA were found only in low titers in 27% of patients with Crohn's disease and in 6% of their relatives. pANCA were not detected in members of healthy families. Only 16% of the patients with ulcerative colitis and their families and none of the patients with primary sclerosing cholangitis and their families were completely negative for pANCA. CONCLUSIONS: These data show that pANCA may be a genetic marker in families of patients with ulcerative colitis and primary sclerosing cholangitis.

Adolescent↗
PubMed1993

Acute pancreatitis in Crohn's disease.

Pancreatitis as an extraintestinal manifestation of Crohn's disease (CD) is controversial. We review the episodes of acute pancreatitis in patients with CD. Of 852 patients, 12 developed clinically overt pancreatitis, representing a frequency of 1.4% in a follow-up period of 10 years. In 10 patients, common causes of pancreatitis were excluded. In 2 patients, drug-induced disease (azathioprine, sulfasalazine) could not be ruled out. Recurrence of pancreatitis was observed in only 2 patients. Younger patients and those with active disease seemed more at risk for development of pancreatitis. If prednisolone was needed for treatment of active CD, no adverse effect was observed for the pancreatitis. Along with the clinical features, we studied autoantibodies against exocrine pancreas; the incidence of autoantibodies in patients with pancreatitis was the same as in the controls who did not develop pancreatic abnormalities. This does not support the hypothesis that acute pancreatitis in CD is associated with the formation of pancreatic autoantibodies.

Acute Disease↗
PubMed1992

Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.

The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction.

Adolescent↗
PubMed1991

Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn's disease.

The presence of antibodies against pancreatic juice (PAB) in patients with Crohn's disease has recently been reported. In our study sera from 273 patients with inflammatory bowel disease (222 with Crohn's disease, 51 with ulcerative colitis) have been examined for PAB and also for antibodies against gut tissues by means of indirect immunofluorescence. PAB were found in 68 of the 222 patients with Crohn's disease (31%), with titres ranging from 1/10 to 1/1280, and in only two patients with ulcerative colitis (4%), with titres of 1/20. None were found in 198 patients with various chronic inflammatory diseases and healthy control subjects. No differences were found between the PAB positive and negative patients when the following parameters were compared: disease activity (Crohn's disease activity index), involvement of bowel segments, incidence of extraintestinal disease, or treatment with anti-inflammatory drugs. Only seven of the patients with Crohn's disease had a history of pancreatic disease and of these, four had detectable pancreatic antibodies. Longitudinal observations of 40 patients with Crohn's disease showed a stable pattern for PAB, independent of disease activity and treatment. Partial characterisation of the PAB antigen, isolated from pancreatic juice, showed a trypsin sensitive macromolecular protein of more than 10(6) daltons not identical with a panel of defined exocrine pancreatic proteins. By contrast, antibodies against goblet cells (GAB) were found in 13 of 51 patients with ulcerative colitis (29%) and in none of the patients with Crohn's disease or control subjects. PAB were found as a highly specific serological marker for Crohn's disease and GAB for ulcerative colitis, but the relevance of PAB and GAB in the pathogenesis in Crohn's disease remains unclear.

Adolescent↗
PubMed1991

Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis.

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases. By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn's disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener's granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes.

Adolescent↗